The products of the cyclooxygenase (prostaglandins, PG) and lipoxygenase (hydroxyeicosatetraenoic acids, HETE; leukotrienes, LT) pathways are important mediators of intraocular inflammation. Little informatrion exists describing their activities in lenses from normal or inflamed eyes. Preliminary results presented in this proposal indicate a marked stimulation of PGE2 synthesis by rabbit lenses from eyes given endotoxin intravitreally. This is the first demonstration of such an effect and it suggests that lens may play a more active role in the inflammatory process than was previously assumed. The objectives of this proposal are to measure the activities of these enzymes in lenses from albino rabbits administered E. coli endotoxin intravitreally (in vivo endotoxin exposure), compare this with the enzymatic activites of lenses exposed to endotoxin in vitro, and determine the effectis of specific inhibitors on the products of these enzymes in the in vivo and in vitro models. De novo synthesis of PGE2 and the stable metabolite of PGI2, 6-keto-PGF1 Alpha, will be determined by radioimmunossay. The synthesis of PG's, HETE's and LT's from 14C-arachidonic acid will be determined by separation of the products in the incubation medium by high-performance liquid chromatography, and quantitation by liquid scintillation spectrometry. The degree of endotoxin-induced inflammation will be determined by slitlamp examination of the eyes for flare, iridal hyperemia and the presence of cells in the anterior chamber. Both cyclooxygenase and lipoxygenase products must be measured since they may exert synergistic effects. For example, vasodilator PG's such as PGE2 and PGI2 may work synergistically with LTB4 to produce inflammatory edema. With basic information on the contribution of lens to the production of these inflammatory mediators, a more complete understanding of the factors involved in intraocular inflammation will be obtained. This information will also provide the basis for future studies such as the role of leukocyte infiltration into the anterior chamber on the metobolism of arachidonic acid (AA) by lens, and the comparative metabolism of AA by lens from normal and cataractous canine eyes.